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First published online February 18, 2004

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PAPPA ensures IGF release

Insulin growth factors (IGFs) are important determinants of fetal growth and development. Pregnancy-associated plasma protein A (PAPPA) modulates the bioavailability and mitogenic activity of IGFs in vitro by regulating the cleavage of the IGF-binding protein, IGFBP4. Conover et al. (p. 1187) now determine the role of PAPPA in vivo and find that it has striking effects on growth during early embryogenesis. They find that PAPPA-null mice are proportional dwarfs, only 60% the size of wild-type mice, with remarkable similarity to IGF2-null mice. Furthermore, PAPPA mRNA colocalises with IGF2 and IGFBP4 transcripts during the development of wild-type embryos. In PAPPA-null mice, IGF2 and IGFBP4 mRNA localisation is unchanged but IGFBP4 is not cleaved and IGF-stimulated mitogenesis is inhibited. Thus, Conover and co-workers provide the first evidence that PAPPA functions as an essential growth regulator by regulating IGF bioavailability during early fetal development.

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Related articles in Development:

Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development

Cheryl A. Conover, Laurie K. Bale, Michael T. Overgaard, Edward W. Johnstone, Ulla H. Laursen, Ernst-Martin Füchtbauer, Claus Oxvig, and Jan van Deursen
Development 2004 131: 1187-1194. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?